Liang Qingnan, Cheng Xuesen, Wang Jun, Owen Leah, Shakoor Akbar, Lillvis John L, Zhang Charles, Farkas Michael, Kim Ivana K, Li Yumei, DeAngelis Margaret, Chen Rui
HGSC, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Cell Genom. 2023 Apr 11;3(6):100298. doi: 10.1016/j.xgen.2023.100298. eCollection 2023 Jun 14.
Cell classes in the human retina are highly heterogeneous with their abundance varying by several orders of magnitude. Here, we generated and integrated a multi-omics single-cell atlas of the adult human retina, including more than 250,000 nuclei for single-nuclei RNA-seq and 137,000 nuclei for single-nuclei ATAC-seq. Cross-species comparison of the retina atlas among human, monkey, mice, and chicken revealed relatively conserved and non-conserved types. Interestingly, the overall cell heterogeneity in primate retina decreases compared with that of rodent and chicken retina. Through integrative analysis, we identified 35,000 distal -element-gene pairs, constructed transcription factor (TF)-target regulons for more than 200 TFs, and partitioned the TFs into distinct co-active modules. We also revealed the heterogeneity of the -element-gene relationships in different cell types, even from the same class. Taken together, we present a comprehensive single-cell multi-omics atlas of the human retina as a resource that enables systematic molecular characterization at individual cell-type resolution.
人类视网膜中的细胞类别高度异质，其丰度相差几个数量级。在这里，我们生成并整合了一份成人人视网膜的多组学单细胞图谱，包括用于单核RNA测序的超过250,000个细胞核和用于单核ATAC测序的137,000个细胞核。对人类、猴子、小鼠和鸡的视网膜图谱进行跨物种比较，发现了相对保守和不保守的类型。有趣的是，与啮齿动物和鸡的视网膜相比，灵长类视网膜中的整体细胞异质性有所降低。通过综合分析，我们鉴定出35,000个远端元件-基因对，为200多个转录因子构建了转录因子（TF）-靶标调控子，并将这些转录因子分为不同的共激活模块。我们还揭示了不同细胞类型（即使是同一类别的细胞类型）中元件-基因关系的异质性。综上所述，我们展示了一份全面的人类视网膜单细胞多组学图谱，作为一种资源，能够在单个细胞类型分辨率下进行系统的分子表征。
